Improving bioproduction through dynamic regulation circuits

Biological production of chemicals and materials is a renewable and economically viable alternative to the current chemical processes, easing the transition towards a biology-based circular economy. The current biomanufacturing industry faces a scalability problem. Frequently, producer strains created in the laboratory do not respond well to industrial conditions (e.g., large fermentation volumes, accumulation of toxic intermediates, media acidification, etc.). The goal of BioCircus is to address the issue caused by the lack of robustness of the engineered microbial strains. BioCircus is based on three main research pillars: (1) the construction of biosensor and dynamic regulation circuits that measure and control the production of the target molecule, (2) the use of machine learning predictive models and automation to improve these circuits and (3) validating the designed strains in pre-industrial conditions, closer than standard molecular biology laboratory procedures to real-world bioproduction operations. Naringenin, a key molecule of the flavonoid family, will be used in as proof-of-principle molecule. E. coli will be used as model organism. The design and construction of biosensors and dynamic regulation circuits controlling naringenin production is expected to support the development of methodologies and tools suitable for any other detectable metabolite. BioCircus will produce academic and industrial impacts that will boost the bioproduction field by enabling a shorter strain time-to-market for a wide variety of adaptive and scalable microbial bioproducer strains.